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Proc Natl Acad Sci U S A. 2014 Jan 28;111(4):1409-14. doi: 10.1073/pnas.1323697111. Epub 2014 Jan 13.

The WNT receptor FZD7 is required for maintenance of the pluripotent state in human embryonic stem cells.

Author information

1
Department of Cellular and Molecular Medicine, Stem Cell Program, University of California, San Diego, La Jolla, CA 92093-0695.

Abstract

WNT signaling is involved in maintaining stem cells in an undifferentiated state; however, it is often unclear which WNTs and WNT receptors are mediating these activities. Here we examined the role of the WNT receptor FZD7 in maintaining human embryonic stem cells (hESCs) in an undifferentiated and pluripotent state. FZD7 expression is significantly elevated in undifferentiated cells relative to differentiated cell populations, and interfering with its expression or function, either by short hairpin RNA-mediated knockdown or with a fragment antigen binding (Fab) molecule directed against FZD7, disrupts the pluripotent state of hESCs. The FZD7-specific Fab blocks signaling by Wnt3a protein by down-regulating FZD7 protein levels, suggesting that FZD7 transduces Wnt signals to activate Wnt/β-catenin signaling. These results demonstrate that FZD7 encodes a regulator of the pluripotent state and that hESCs require endogenous WNT/β-catenin signaling through FZD7 to maintain an undifferentiated phenotype.

KEYWORDS:

differentiation; human pluripotent stem cell; self-renewal

PMID:
24474766
PMCID:
PMC3910637
DOI:
10.1073/pnas.1323697111
[Indexed for MEDLINE]
Free PMC Article

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